Executive Control and the Prefrontal Cortex
Executive control is the ability to guide thought and action in accordance with internal goals. One of the great mysteries of neuroscience concerns how this capacity for coordinated, purposeful behavior arises from neural states. Decades of cognitive and neuroscientific research have focused on the mechanisms by which executive control guides behavior and the brain structures upon which these functions depend, such as the prefrontal cortex (PFC), anterior cingulate cortex, basal ganglia and brainstem neuromodulatory systems. However, the functional contribution of these regions and their interactive role in the coordination of cognitive, social and affective processes remain to be well characterized. A major goal of our research is to understand the prefrontal networks underlying executive control, investigating the functional profile and topography of lateral and orbitofrontal sectors of PFC.
Lateral Prefrontal Cortex
Accumulating neuroscience evidence indicates that lateral PFC exhibits three properties that are central to executive control: (1) the representational coding scheme of this region conveys information about internal behavioral goals and/or prior temporal context; (2) these representations can be actively maintained over time in a highly accessible form (i.e., storage of information via sustained neuronal activity patterns); and (3) the output of this region is an activation signal that biases the flow of ongoing processing in other brain regions, such as those responsible for perception, action selection, memory retrieval and emotional evaluation. Additionally, the neurotransmitter dopamine plays a key modulatory role over lateral PFC function by regulating the way that goal representations are maintained and updated. These findings elucidate the architecture of executive control in lateral PFC and suggest that this region may represent a necessary component of the neural systems for goal-directed behavior.
Our research has investigated this hypothesis by studying human brain lesion patients with focal damage to the dorsolateral PFC, examining whether this region is necessary for performance on neuropsychological tests of executive control (Delis-Kaplan Executive Function System) and broader tests of general intelligence (Wechsler Adult Intelligence Scale) (Barbey et al., in press a). The results of this research indicate that: (1) patients with focal dorsolateral PFC damage exhibit lower scores, at the latent variable level, than controls in general intelligence (g) and executive function; (2) dorsolateral PFC patients demonstrate lower scores than controls in several executive measures; and (3) these latter differences are no longer significant when the pervasive influence of the general factor of intelligence (g) is statistically removed. Taken together, these findings indicate that the dorsolateral PFC is a central component of the neural systems underlying global aspects of general intelligence and suggest that this region provides a unified neural architecture for higher cognitive functions.
We have also actively investigated the role of the dorsolateral PFC in executive control processes for working memory, administering the Wechsler Memory Scale and N-Back Task to patients with focal dorsolateral PFC lesions (Barbey et al., in press b). Dorsolateral PFC damage was associated with deficits in the manipulation of verbal and spatial knowledge, with left dlPFC necessary for manipulatinginformation in working memory (letter-number sequencing) and right dlPFC critical for manipulating information in a broader range of reasoning contexts (arithmetic, matrix reasoning). The results provide key neuropsychological evidence for the necessity of the dorsolateral PFC in domain-general mechanisms for the manipulation of verbal and spatial knowledge. The diverse control functions mediated by this region suggest that its neurons adaptively code information for the control of behavior in a broad range of contexts, and support new approaches to understanding the evolution and development of PFC function based on the adaptive re-use of existing neural circuits (e.g., employing dorsolateral PFC to support the spectrum of control functions underlying goal-directed behavior).
Increasing neuroscience evidence suggests that orbitofrontal cortex provides a nexus for sensory integration, enabling the coordination of cognitive, social and affective representations in executive control. Our research has investigated the necessity of this region for executive control processes in working memory, administering the Wechsler Memory Scale and N-Back Task to patients with focal orbitofrontal cortex lesions (Barbey et al., 2011). The results of this study indicate that damage to medial orbitofrontal cortex is associated with reliable deficits in working memory (relative to patients with lateral orbitofrontal cortex lesions). Selective impairment was observed on neuropsychological tests of the joint maintenance, monitoring and manipulation of representations in working memory (N-Back), with intact performance on pure tests of working memory maintenance (Digit/Spatial Span Forward) and manipulation (Digit/Spatial Span Backward, Letter-Number Sequencing). These findings contribute to an emerging empirical case for the involvement of medial orbitofrontal cortex in the coordination of multiple cognitive operations, suggesting that this region is engaged when the integration of two or more separate cognitive operations is required for goal achievement.
Our current research further examines the functional networks underlying executive control, providing lesion evidence for a distributed fronto-parietal circuit that principally involves dorsolateral PFC and superior parietal cortex (Barbey et al., in press c ; Koenigs et al., 2009). We have investigated the neural substrates of the general factor of intelligence (g) and executive function in 182 patients with focal brain lesions using voxel-based lesion-symptom mapping (Barbey et al., in press c). We observed a significant effect on g and executive function with lesions in left hemispheric white matter sectors including the superior longitudinal/arcuate fasciculus that connect frontal and parietal cortices. Despite its distributed nature, the neural substrates of g and executive function were remarkably circumscribed, concentrated in the core of white matter, and comprising a narrow subset of regions associated with performance on individual Wechsler Adult Intelligence Scale (WAIS) and Delis-Kaplan Executive Function System (D-KEFS) subtests. The largest overlap between WAIS subtests and g was found for Verbal Comprehension and Working Memory, and for executive function measures of the D-KEFS (i.e., Trail Making, Verbal Fluency, Card Sorting, and Twenty Questions). Collectively, these subtests assess verbal knowledge about the world, verbal reasoning, working memory capacity, as well as cognitive flexibility and executive control, and are associated with a distributed fronto-parietal network. This suggests that g and executive function draw on the combination of conceptual knowledge and executive processes, and that the communication between areas associated with these capacities is of critical importance.
The observed findings contribute to a growing body of neuropsychological patient evidence indicating that damage to a distributed network of frontal and parietal regions is associated with impaired performance on tests of general intelligence (Gläscher et al., 2010, 2009; Chiang et al., 2009; Colom & Thompson, 2011; Colom et al., 2009; Jung & Haier, 2007). A recent study by Gläscher and colleagues (2010) applied voxel-based lesion-symptom mapping to elucidate the neural substrates of psychometric g, reporting a left lateralized fronto-parietal network that converges with the observed pattern of findings and further supports the role of this network in components of general intelligence that draw upon conceptual knowledge and working memory. Our findings advance this line of research by elucidating the relationship between general intelligence and executive function – demonstrating that these domains recruit a highly overlapping and broadly distributed network of frontal and parietal regions.
The fronto-parietal network identified by the present analysis includes lateral frontopolar cortex, anterior PFC, dorsolateral PFC, anterior cingulate/medial PFC, and the inferior and superior parietal lobe. This constellation of regions is commonly engaged by tasks that require executive control processes (for reviews, see Botvinick et al. 2004; Dosenbach et al. 2007; Gruber & Goshke 2004; Ramnani & Owen 2004). The fronto-parietal network is recruited by paradigms that elicit controlled processing related to the simultaneous consideration of multiple interdependent contingencies (Kroger et al. 2002), conflicting stimulus-response mappings (Crone et al. 2006), and integrating working memory with attentional resource allocation (Koechlin et al. 1999). In addition, many of the regions in the fronto-parietal network show sustained activity over the duration of a task block (Dosenbach et al. 2006; Velanova et al. 2003; Yarkoni et al. 2005), supporting the maintenance and integration of items for goal-directed behavior.
The observed pattern of findings supports the proposal that the fronto-parietal network provides a unified architecture for the integration and control of cognitive representations. According to this framework, processes for integration and control are critical for the optimal recruitment of internal resources to exhibit goal-directed behavior – supporting conceptual representations and executive processes that provide the basis for high-level cognition. We propose that mechanisms for integration and control are carried out by a central system that has extensive access to sensory and motor representations (cf., Miller & Cohen, 2001) and that the fronto-parietal network is at an ideal site in the brain to support these functions. Nodes of this network are thoroughly and reciprocally connected with each other, as well as with other association cortices and subcortical areas, a property that allows widespread access to perceptual and motor representations at multiple levels. With this unique connectivity pattern, and specialization in a wide variety of high-level processes, the fronto-parietal network can function as a source of integration and top-down control in the brain. This framework therefore complements existing neuroscience models by highlighting the importance of the white-matter association tracts (e.g., the arcuate fasciculus) for the integration of cognitive representations in general intelligence (Jung & Haier, 2007), while also emphasizing the central role of top-down mechanisms within frontal and parietal cortices for the executive control of behavior (Miller & Cohen, 2001). According to this framework, the fronto-parietal network is a core system that supports the integration and control of distributed patterns of neural activity throughout the brain, providing a unified architecture for general intelligence and executive function.